Chromosome-Centric Look at the Genome

Iourov, Ivan Y.; Yurov, Yuri B.; Vorsanova, Svetlana G.

doi:10.1007/978-3-030-62532-0_9

Cited by 4 publications

(4 citation statements)

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“…Chromosomal abnormalities and CNVs represent an important, albeit poorly explored, genetic causes of epilepsy [13,14,21]. The problem of lacking cytogenetic and cytogenomic studies of epilepsy is likely to arise from general decrease in cytogenetic competence [144]. It has been systematically reported that ignoring chromosomal approaches to solving genomic biomedical problems lead to incomplete understanding of mechanisms for genetic diseases [144][145][146].…”

Section: Discussionmentioning

confidence: 99%

“…The problem of lacking cytogenetic and cytogenomic studies of epilepsy is likely to arise from general decrease in cytogenetic competence [144]. It has been systematically reported that ignoring chromosomal approaches to solving genomic biomedical problems lead to incomplete understanding of mechanisms for genetic diseases [144][145][146]. The formation of our consortium is basically aimed at incorporating cytogenomic variations to the complemented view of genetic causes of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

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Cytogenomic epileptology

et al. 2023

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Molecular cytogenetic and cytogenomic studies have made a contribution to genetics of epilepsy. However, current genomic research of this devastative condition is generally focused on the molecular genetic aspects (i.e. gene hunting, detecting mutations in known epilepsy-associated genes, searching monogenic causes of epilepsy). Nonetheless, chromosomal abnormalities and copy number variants (CNVs) represent an important part of genetic defects causing epilepsy. Moreover, somatic chromosomal mosaicism and genome/chromosome instability seem to be a possible mechanism for a wide spectrum of epileptic conditions. This idea becomes even more attracting taking into account the potential of molecular neurocytogenetic (neurocytogenomic) studies of the epileptic brain. Unfortunately, analyses of chromosome numbers and structure in the affected brain or epileptogenic brain foci are rarely performed. Therefore, one may conclude that cytogenomic area of genomic epileptology is poorly researched. Accordingly, molecular cytogenetic and cytogenomic studies of the clinical cohorts and molecular neurocytogenetic analyses of the epileptic brain appear to be required. Here, we have performed a theoretical analysis to define the targets of the aforementioned studies and to highlight future directions for molecular cytogenetic and cytogenomic research of epileptic disorders in the widest sense. To succeed, we have formed a consortium, which is planned to perform at least a part of suggested research. Taking into account the nature of the communication, “cytogenomic epileptology” has been introduced to cover the research efforts in this field of medical genomics and epileptology. Additionally, initial results of studying cytogenomic variations in the Russian neurodevelopmental cohort are reviewed with special attention to epilepsy. In total, we have concluded that (i) epilepsy-associated cytogenomic variations require more profound research; (ii) ontological analyses of epilepsy genes affected by chromosomal rearrangements and/or CNVs with unraveling pathways implicating epilepsy-associated genes are beneficial for epileptology; (iii) molecular neurocytogenetic (neurocytogenomic) analysis of postoperative samples are warranted in patients suffering from epileptic disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytogenomic epileptology

et al. 2023

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“…Knowledge is not a usual term for designating elements of data analysis in medical genomics. Taking into account suggested complexity of epistemological aspects of genomic data analysis as well as extreme variability of genomic ontologies [1,2], it is not surprising that researchers prefer to focus on specific tasks such as comparative analysis of genomic variations in different cohorts, selection of single causative mutations or evaluating functional consequences of detected sequence variants [3][4][5]. On the other hand, results of numerous studies dedicated to uncovering genomic variations associated with diseases and massive sets of data on gene ontologies [2,[6][7][8][9] appear to be useful for developing knowledge-based approaches to determine the consequences of genomic changes.…”

Section: Introductionmentioning

confidence: 99%

Knowledge-Based Prioritization of Genomic Variations: A Quest for Detailed Understanding the Genetic Architecture of Diseases

Iourov

2023

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Understanding the genetic architecture of a disease is crucial for development of valid diagnostic and therapeutic interventions. The analysis of genomic variations associated with pathological conditions is the starting point for uncovering disease-causing pathways (candidate processes). However, the complexity of intergenic and genetic-environmental interactions hinders the identification of pathogenic values of genomic changes. Furthermore, heredity, epigenetics and somatic mosaicism make the interpretation of genomic data even more sophisticated. To succeed, a variety of bioinformatic techniques are applied. Here, reviewing own and literature data, knowledge-based prioritization of genomic variations is described. Theoretical basis of the knowledge-based prioritization is given with a special regard to gene ontology, heuristics, hermeneutics (genomic hermeneutics) and analytics. Practical and methodological issues of prioritization using ontology- or pathway-based systems analysis are considered in the light of optimistic and realistic scenarios of cumulative phenotypic effects of the variome (the whole set of genomic variations in an individual or specific set of genomic variations for a phenotypic outcome). In the present communication, copy number variants (CNVs) in children with neurodevelopmental diseases are used as a practical foundation for the prioritization, inasmuch as these genome variations are systematically overlooked in the so-called NGS era. Nonetheless, it is highly likely that the prioritization is applicable to almost all types of genomic variations (e.g. chromosome abnormalities, gene mutations, functional synonymous variants etc.). The present methodology seems to be a valuable addition to current biomedical science widening the opportunities for medical genomics and genetics.

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“…Her original ideas about current role of cytogenetics in bioscience were repeatedly expressed. She consistently signalized numerous problems in the field and proposed the ways to solve these problems [115][116][117][118][119][120][121][122][123]. It is certain that her ideas should not be forgotten.…”

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confidence: 99%